In addition to the well characterized HLA-DR system, two other human B cell alloantigen systems, MB and MT, have recently been described. The MB and MT antigens are HLA-linked, but it is still not known whether these antigens represent the products of loci distinct from HLA-DR. Each MB or MT specificity is associated with two or three DR specificities: MB1 is associated with DR1, DR2, and DRw6; MB2 with DR3 and DR7; MB3 with DR4 and DR5; MT1 with DR1, DR2, and DRw6; MT2 with DR3, DR5, and DRw6; and MT3 with DR4 and DR7. The finding that MB1 and MT2 occur with significantly increased frequencies in patients with systemic lupus erythematosus and primary sicca syndrome has suggested that these antigens may be involved in the genetic predisposition to the development of these diseases. Recent studies by other workers suggest that the MT and MB molecules may differ structurally from HLA-DR molecules and, therefore, may be products of loci distinct from HLA-DR. My previous work suggests that the MB1 and MT2 antigenic determinants are located on the same molecules as the DR antigenic determinants and that immunoprecipitated MB1 and DR2 molecules from the same individual are structurally similar. The proposed studies will employ immunochemical techniques to elucidate the molecular relationship of the MB, MT, and HLA-DR systems in an effort to establish the molecular basis for B cell antigen-disease associations. These techniques include sequential immunoprecipitation experiments, two-dimensional gel electrophoresis, and tryptic peptide mapping by high pressure liquid chromatography. This approach differs from the work of other investigators in that it employs alloantisera (instead of xenoantisera) and antigens isolated from peripheral blood lymphocytes in addition to B lymphoblastoid cell lines.